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Chronic high-rate pacing induces heart failure with preserved ejection fraction-like phenotype in Ossabaw swine.
Tune, Johnathan D; Goodwill, Adam G; Baker, Hana E; Dick, Gregory M; Warne, Cooper M; Tucker, Selina M; Essajee, Salman I; Bailey, Chastidy A; Klasing, Jessica A; Russell, Jacob J; McCallinhart, Patricia E; Trask, Aaron J; Bender, Shawn B.
Afiliación
  • Tune JD; Department of Physiology and Anatomy, University of North Texas Health Science Center, 3500 Camp Bowie Blvd., Fort Worth, TX, 76107, USA. johnathan.tune@unthsc.edu.
  • Goodwill AG; Department of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, OH, USA.
  • Baker HE; Diabetes and Complications Research, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA.
  • Dick GM; Department of Physiology and Anatomy, University of North Texas Health Science Center, 3500 Camp Bowie Blvd., Fort Worth, TX, 76107, USA.
  • Warne CM; Department of Physiology and Anatomy, University of North Texas Health Science Center, 3500 Camp Bowie Blvd., Fort Worth, TX, 76107, USA.
  • Tucker SM; Department of Physiology and Anatomy, University of North Texas Health Science Center, 3500 Camp Bowie Blvd., Fort Worth, TX, 76107, USA.
  • Essajee SI; Department of Physiology and Anatomy, University of North Texas Health Science Center, 3500 Camp Bowie Blvd., Fort Worth, TX, 76107, USA.
  • Bailey CA; Department of Biomedical Sciences, University of Missouri, Columbia, MO, USA.
  • Klasing JA; Research Service, Harry S. Truman Memorial Veterans Hospital, Columbia, MO, USA.
  • Russell JJ; Department of Biomedical Sciences, University of Missouri, Columbia, MO, USA.
  • McCallinhart PE; Research Service, Harry S. Truman Memorial Veterans Hospital, Columbia, MO, USA.
  • Trask AJ; Department of Biomedical Sciences, University of Missouri, Columbia, MO, USA.
  • Bender SB; Research Service, Harry S. Truman Memorial Veterans Hospital, Columbia, MO, USA.
Basic Res Cardiol ; 117(1): 50, 2022 10 12.
Article en En | MEDLINE | ID: mdl-36222894
The lack of pre-clinical large animal models of heart failure with preserved ejection fraction (HFpEF) remains a growing, yet unmet obstacle to improving understanding of this complex condition. We examined whether chronic cardiometabolic stress in Ossabaw swine, which possess a genetic propensity for obesity and cardiovascular complications, produces an HFpEF-like phenotype. Swine were fed standard chow (lean; n = 13) or an excess calorie, high-fat, high-fructose diet (obese; n = 16) for ~ 18 weeks with lean (n = 5) and obese (n = 8) swine subjected to right ventricular pacing (180 beats/min for ~ 4 weeks) to induce heart failure (HF). Baseline blood pressure, heart rate, LV end-diastolic volume, and ejection fraction were similar between groups. High-rate pacing increased LV end-diastolic pressure from ~ 11 ± 1 mmHg in lean and obese swine to ~ 26 ± 2 mmHg in lean HF and obese HF swine. Regression analyses revealed an upward shift in LV diastolic pressure vs. diastolic volume in paced swine that was associated with an ~ twofold increase in myocardial fibrosis and an ~ 50% reduction in myocardial capillary density. Hemodynamic responses to graded hemorrhage revealed an ~ 40% decrease in the chronotropic response to reductions in blood pressure in lean HF and obese HF swine without appreciable changes in myocardial oxygen delivery or transmural perfusion. These findings support that high-rate ventricular pacing of lean and obese Ossabaw swine initiates underlying cardiac remodeling accompanied by elevated LV filling pressures with normal ejection fraction. This distinct pre-clinical tool provides a unique platform for further mechanistic and therapeutic studies of this highly complex syndrome.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Insuficiencia Cardíaca Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Basic Res Cardiol Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Alemania
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Insuficiencia Cardíaca Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Basic Res Cardiol Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Alemania